Mechanisms of smooth muscle contraction elicited by cationic proteins in guinea pig trachealis. Strek, Mary E., Felicia S. Williams, Gerald J. Gleich, Alan R. Leff, and Steven R. White. Section of Pulmonary and Critical Care Medicine, Department of Medicine, and the Committees on Clinical Pharmacology and Cell Physiology, Division of the Biological Sciences, The University of Chicago, Chicago, Illinois 60637; and Departments of Immunology and Medicine, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905
APStracts 2:0172L, 1995.
Cationic proteins elicit contraction of airway smooth muscle, but the mechanisms by which this occurs is not completely understood. We studied the potential mechanisms by which eosinophil major basic protein (MBP), poly-l-lysine (PL), and poly-l-arginine (PA) cause contraction of isolated guinea pig tracheal smooth muscle in vivo. Topical application of 10-8 mol/cm2 MBP to the tracheal smooth muscle segment caused 0.74 +/- 0.11 g/cm maximum active tension (P = 0.0004 vs baseline, n = 9); buffer control caused minimal contractile response (0.24 +/- 0.06 g/cm maximum active tension, P = 0.004 vs MBP, n = 8). Both 10-8 mol/cm2 PL (n = 8) and 10-8 mol/cm2 PA (n = 6) applied topically caused contraction of guinea pig trachealis (0.95 +/- 0.24 g/cm active tension for PL, P = 0.006 vs baseline, and 0.59 +/- 0.10 g/cm active tension for PA, P = 0.003 vs baseline). Pretreatment of the guinea pig with 1.5 mg/kg atropine intravenously (iv) blocked the subsequent response to MBP (0.27 +/- 0.10 g/cm active tension, P = 0.007 vs MBP alone, n = 7). In contrast, contraction of the guinea pig trachealis in response to either PL or PA was not affected by atropine pretreatment. Tracheal smooth muscle contraction elicited by either MBP or PL were blocked by pretreatment with 20 mg/kg indomethacin (INDO) iv (0.11 +/- 0.17 g/cm active tension for MBP + INDO, P = 0.0009 vs MBP alone, n = 6, and 0.29 +/- 0.11 g/cm active tension for PL + INDO, P = 0.03 vs PL alone, n = 6). Pretreatment with INDO did not block the subsequent response to PA, however. We demonstrate that MBP causes contraction of guinea pig tracheal smooth muscle both through stimulation of the parasympathetic nervous system and secre tion of a product of the cyclooxygenase pathway. Neither PL nor PA, while of similar molecular weight and charge as MBP, cause tracheal smooth muscle contraction via the parasympathetic nervous system, though some cationic proteins may act via a prostanoid mediator. Thus, the cationic charge of MBP is not solely responsible for its effects on tracheal smooth muscle in the guinea pig. 

Received 7 November 1994; accepted in final form 8 August 1995.
APS Manuscript Number L321-4.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 31 October 95